Imipenem-Cilastatin Sodium
**Imipenem-cilastatin** is a potent, broad-spectrum intravenous/intramuscular antimicrobial combination reserved for serious, life-threatening, or multi-drug resistant infections in veterinary medicine. * **Imipenem** is a carbapenem antibiotic with an exceptionally broad spectrum of activity, including gram-positive, gram-negative, and anaerobic bacteria. It is particularly valuable against resistant gram-negative organisms like *Pseudomonas aeruginosa* and Enterobacteriaceae (e.g., ESBL-producing strains). * **Cilastatin** is a dehydropeptidase I (DHP I) inhibitor. It has no antibacterial activity itself but is crucial because it prevents the rapid degradation of imipenem by enzymes in the kidneys. > **Clinical Pearl:** Because of its broad spectrum and importance in treating highly resistant infections, imipenem is considered a "big gun" or reserve antibiotic. Its use should ideally be guided by culture and susceptibility testing to prevent the emergence of carbapenem-resistant bacteria.
Mechanism: The drug functions through a synergistic two-part mechanism: 1. **Imipenem (Bactericidal Action):** Imipenem penetrates bacterial cell envelopes and binds with high affinity to **penicillin-binding proteins (PBPs)** (specifically PBP-2 and PBP-1B in gram-negative bacteria) โ inhibits peptidoglycan cross-linking โ disrupts bacterial cell wall synthesis โ leads to cell lysis and death. 2. **Cilastatin (Pharmacokinetic Enhancer):** Imipenem is normally rapidly metabolized by **dehydropeptidase I (DHP I)**, an enzyme located on the brush borders of the proximal renal tubules. Cilastatin competitively inhibits **DHP I** โ prevents imipenem degradation โ ensures high, therapeutic antibacterial concentrations in the urine and protects the patient from proximal renal tubular necrosis that can occur if imipenem is administered alone.
Dosing by species
- Susceptible infections ยท 5-10 mg/kg ยท IV, SC or IM ยท q8h ยท IM form is different
- Susceptible infections ยท 5-10 mg/kg ยท IV or IM ยท q6h ยท IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
- Tissue infections ยท 3-7.5 mg/kg ยท IV, SC or IM ยท q4-6h ยท 3-5 days
- Sepsis, more resistant organisms ยท 5 mg/kg ยท IV ยท q4h ยท 3-5 days ยท Multi-drug resistant bacteria may require q2h dosing
- Treatment of Nocardiosis ยท 2-5 mg/kg ยท IV ยท q8h
- Susceptible infections (Adult horses) ยท 10-20 mg/kg ยท IV ยท q6h ยท Give via slow IV over a 10 minute period. Alternatively, a CRI of 16 micrograms/kg/minute should maintain synovial concentrations > 1 microgram/mL.
- Susceptible infections (Foals) ยท 10-20 mg/kg ยท IV ยท q6h
- Susceptible infections (Foals) ยท 10-15 mg/kg ยท IV or IM ยท q6-12h ยท IM if diluted into 1% lidocaine. May give as a CRI at 0.4-0.8 mg/kg/hr.
- Susceptible infections ยท 5-10 mg/kg ยท IV, SC or IM ยท q8h ยท IM form is different
- Susceptible infections ยท 5-10 mg/kg ยท IV or IM ยท q6h ยท IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
Routes of administration
Contraindications
- Patients with known hypersensitivity to imipenem, cilastatin, or other beta-lactam antibiotics (due to partial cross-reactivity)
- Caution in patients with renal impairment (dosage adjustment required)
- Caution in patients with underlying CNS disorders (e.g., seizures, head trauma) due to increased risk of neurotoxicity
Adverse effects
- Gastrointestinal upset (vomiting, anorexia, diarrhea)
- CNS toxicity (seizures, tremors)
- Hypersensitivity reactions (pruritus, fever, anaphylaxis)
- Infusion reactions (thrombophlebitis)
- Severe pain and potential neurovascular damage at IM injection sites
- Transient increases in BUN, serum creatinine, AST, ALT, and Alkaline Phosphatase
- Hypotension or tachycardia (rare)
Drug interactions
- Aminoglycosides ยท Additive effects or synergy may result, particularly against Enterococcus, Staph. aureus, and Listeria monocytogenes. No synergy or antagonism noted against Enterobacteriaceae or Pseudomonas aeruginosa.
- Beta-Lactam Antibiotics ยท Antagonism may occur against several Enterobacteriaceae (including Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia). Concurrent use is not recommended.
- Chloramphenicol ยท May antagonize the antibacterial effects of imipenem (based on in vitro evidence).
- Probenecid ยท May increase concentrations and elimination half-life of cilastatin, but not imipenem; concurrent use is not recommended.
- Trimethoprim/Sulfa ยท Synergy may occur against Nocardia asteroides when used in combination.
Monitoring
- Clinical efficacy (resolution of infection signs)
- Adverse effects (especially CNS signs like tremors or seizures)
- Renal and hepatic function tests (BUN, creatinine, AST, ALT, Alk Phos) if treatment is prolonged or if the patient has pre-existing organ dysfunction
Overdose
Information on acute toxicity is limited. The LD50 of imipenem:cilastatin (1:1 ratio) in mice and rats is approximately 1 gram/kg/day. **Management:** * Halt therapy immediately. * Provide supportive and symptomatic care (e.g., anticonvulsants if seizures occur, fluid therapy to support renal clearance).
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.